Excessive weight gain with antipsychotic drug treatment may be tied to certain genetic variants, according to a small initial study published in the journal Archives of General Psychiatry.

Antipsychotic medications are the first line of treatment for schizophrenia and other serious mental disorders. Although they help control psychotic symptoms, they may carry serious metabolic side effects that can result in significant weight gain and cardiovascular problems.

Some people on these medications seem more susceptible to severe weight gain than others, but it has been difficult to predict who is most vulnerable.

Anil Malhotra, M.D., of the Feinstein Institute for Medical Research on Long Island, N.Y., and colleagues set out to identify any common gene variants associated with antipsychotic-induced weight gain in a group of patients who had never before taken the drugs. The participants were monitored closely to make sure they continued taking the medication during the study period.

The first group included 139 pediatric patients who were prescribed a second-generation antipsychotic. Over a period of 12 weeks, patients were examined to continually assess weight and metabolic effects of the medications.

The researchers conducted similar assessments of three small groups of adult patients also prescribed second-generation antipsychotics.

The researchers found markers in a gene called the melanocortin 4 receptor (MC4R) that were linked to extreme weight gain in those prescribed second generation antipsychotics.

The MC4R region overlaps somewhat with another region already known to be associated with obesity in the general population. These results were consistent among the three independent groups of patients.

The results have potential clinical implications. Patients with the identified gene variants that would predispose them to severe weight gain while taking an antipsychotic drug eventually could be offered alternative treatments, especially those who do not have a psychotic disorder.

Although particular gene variants were pinpointed in this study, it was conducted on a relatively small group of participants. Further research with larger samples is needed to confirm the results.